A Specialized Program of Research Excellence for patients with cancer of the head and neck entitled 'The[unreadable] Molecular Basis of Head and Neck Cancer Biology, Treatment and Prevention" is proposed that will[unreadable] significantly improve treatment results and reduce morbidity and mortality associated with this devastating[unreadable] malignancy. These goals will be achieved through improved understanding and application of molecular[unreadable] biology to the detection, prevention, treatment selection and development of new therapies for patients with[unreadable] head and neck cancers. Our ongoing hypothesis is that increased understanding of the molecular basis for[unreadable] treatment will allow more precise individualized patient selection that will result in less morbid therapy and[unreadable] improved quality of life, in addition to the possibility of better control of metastases and earlier detection or[unreadable] prevention of second primary malignancies.[unreadable] We propose continuation of this integrated translational research program consisting of four major projects[unreadable] that explore 1.) more specific treatment selection for patients likely to be cured with radiation or[unreadable] chemotherapy; 2.) new small molecule inhibitors of apoptosis-regulation to increase chemo/radiosensitivity;[unreadable] 3.) improved survival through development of sound prevention strategies; and 4.) the role of critical small[unreadable] molecules and chemoradiation sequencing for optimizing treatment results. These major translational[unreadable] projects are complemented by ongoing highly successful Career Development and Developmental Research[unreadable] Programs. All SPORE studies are supported by three Core Resources with demonstrated success in our[unreadable] initial funding period (Administration and Translational Trials Support, Biostatistics, and Tissue and[unreadable] Histopathology). Emphasis is placed on continued ongoing scientific review of all programs and core[unreadable] resources through utilization of an established Operations Committee, Senior Advisory Council and External[unreadable] Review Committee comprised of expert basic and clinician scientists in the field of cancer research. Strong[unreadable] institutional commitment in our initial funding period has been increased significantly in this renewal[unreadable] application to support equipment needs, our Developmental Research Program and provide increased[unreadable] flexibility to pursue further investigations of novel discoveries that are made as a result of these SPORE[unreadable] projects and collaborations. This Head and Neck SPORE is a fully integrated component of the University of[unreadable] Michigan Comprehensive Cancer Center. We have incorporated extensive use of Cancer Center core[unreadable] facilities and clinical and laboratory resources, and we draw heavily on experienced Cancer Center[unreadable] leadership. Superb teams of experienced clinical / basic collaborators combined with high institutional[unreadable] commitment and priority, and extensive patient resources provide an outstanding research environment that[unreadable] will ensure continued success in achieving overall SPORE goals.